Background:Current protein biomarkers are only moderately predictive at identifying individuals with mild traumatic brain injury or concussion.Therefore,more accurate diagnostic markers are needed for sport-related co...Background:Current protein biomarkers are only moderately predictive at identifying individuals with mild traumatic brain injury or concussion.Therefore,more accurate diagnostic markers are needed for sport-related concussion.Methods:This was a multicenter,prospective,case-control study of athletes who provided blood samples and were diagnosed with a concussion or were a matched non-concussed control within the National Collegiate Athletic Association-Department of Defense Concussion Assessment,Research,and Education Consortium conducted between 2015 and 2019.The blood was collected within 48 h of injury to identify protein abnormalities at the acute and subacute timepoints.Athletes with concussion were divided into 6 h post-injury(0-6 h post-injury)and after 6 h postinjury(7-48 h post-injury)groups.We applied a highly multiplexed proteomic technique that used a DNA aptamers assay to target 1305proteins in plasma samples from athletes with and without sport-related concussion.Results:A total of 140 athletes with concussion(79.3%males;aged 18.71±1.10 years,mean±SD)and 21 non-concussed athletes(76.2%males;19.14±1.10 years)were included in this study.We identified 338 plasma proteins that significantly differed in abundance(319 upregulated and 19 downregulated)in concussed athletes compared to non-concussed athletes.The top 20 most differentially abundant proteins discriminated concussed athletes from non-concussed athletes with an area under the curve(AUC)of 0.954(95%confidence interval:0.922-0.986).Specifically,after 6 h of injury,the individual AUC of plasma erythrocyte membrane protein band 4.1(EPB41)and alpha-synuclein(SNCA)were 0.956 and 0.875,respectively.The combination of EPB41 and SNCA provided the best AUC(1.000),which suggests this combination of candidate plasma biomarkers is the best for diagnosing concussion in athletes after 6 h of injury.Conclusion:Our data suggest that proteomic profiling may provide novel diagnostic protein markers and that a combination of EPB41 and SNCA is the most predictive biomarker of concussion after 6 h of injury.展开更多
Introduction Patients who had a mild ischaemic stroke who present with subtle or resolving symptoms sometimes go undiagnosed,are excluded from treatment and in some cases clinically worsen.Circulating immune cells are...Introduction Patients who had a mild ischaemic stroke who present with subtle or resolving symptoms sometimes go undiagnosed,are excluded from treatment and in some cases clinically worsen.Circulating immune cells are potential biomarkers that can assist with diagnosis in ischaemic stroke.Understanding the transcriptomic changes of each cell population caused by ischaemic stroke is critical because they work closely in a complicated relationship.In this study,we investigated peripheral blood mononuclear cells(PBMCs)transcriptomics of patients who had a stroke using a single-cell RNA sequencing to understand peripheral immune response after mild stroke based on the gene expression in an unbiased way.Methods Transcriptomes of PBMCsfrom 10 patients who had an acute ischaemic stroke within 24 hours after stroke onset were compared with 9 race-matched/age-matched/gender-matched controls.Individual PBMCs were prepared with ddSeqTM(Illumina-BioRad)and sequenced on the Illumina NovaSeq 6000 platform.Results Notable population changes were observed in patients who had a stroke,especially in NK cells and CD14+monocytes.The number of NK cells was increased,which was further confirmed by flow cytometry.Functional analysis implied that the activity of NK cells also is enhanced in patients who had a stroke.CD14+monocytes were clustered into two groups;dendritic cell-related CD14+monocytes and NK cell-related CD14+monocytes.We found CD14+monocyte subclusters were dramatically reduced in patients who had a stroke.Discussion This is the first study demonstrating the increased number of NK cells and new monocyte subclusters of mild ischaemic stroke based on the transcriptomic analysis.Our findings provide the dynamics of circulating immune response that could assist diagnosis and potential therapeutic development of mild ischaemic stroke.展开更多
基金supported by the Grand Alliance CARE Consortiumfunded in part by the National Collegiate Athletic Association(NCAA)+1 种基金the Department of Defense(DoD).supported by the Office of the Assistant Secretary of Defense for Health Affairs,through the Combat Casualty Care Research Program,endorsed by the Department of Defense,under Award No.W81XWH1420151。
文摘Background:Current protein biomarkers are only moderately predictive at identifying individuals with mild traumatic brain injury or concussion.Therefore,more accurate diagnostic markers are needed for sport-related concussion.Methods:This was a multicenter,prospective,case-control study of athletes who provided blood samples and were diagnosed with a concussion or were a matched non-concussed control within the National Collegiate Athletic Association-Department of Defense Concussion Assessment,Research,and Education Consortium conducted between 2015 and 2019.The blood was collected within 48 h of injury to identify protein abnormalities at the acute and subacute timepoints.Athletes with concussion were divided into 6 h post-injury(0-6 h post-injury)and after 6 h postinjury(7-48 h post-injury)groups.We applied a highly multiplexed proteomic technique that used a DNA aptamers assay to target 1305proteins in plasma samples from athletes with and without sport-related concussion.Results:A total of 140 athletes with concussion(79.3%males;aged 18.71±1.10 years,mean±SD)and 21 non-concussed athletes(76.2%males;19.14±1.10 years)were included in this study.We identified 338 plasma proteins that significantly differed in abundance(319 upregulated and 19 downregulated)in concussed athletes compared to non-concussed athletes.The top 20 most differentially abundant proteins discriminated concussed athletes from non-concussed athletes with an area under the curve(AUC)of 0.954(95%confidence interval:0.922-0.986).Specifically,after 6 h of injury,the individual AUC of plasma erythrocyte membrane protein band 4.1(EPB41)and alpha-synuclein(SNCA)were 0.956 and 0.875,respectively.The combination of EPB41 and SNCA provided the best AUC(1.000),which suggests this combination of candidate plasma biomarkers is the best for diagnosing concussion in athletes after 6 h of injury.Conclusion:Our data suggest that proteomic profiling may provide novel diagnostic protein markers and that a combination of EPB41 and SNCA is the most predictive biomarker of concussion after 6 h of injury.
基金supported by the Intramural Research Program of the National Institutes of Health/National Institute of Neurological Disorders and Stroke and National Institute of Nursing Research(NIH ZIANS003043 and NIH ZIANR000015).
文摘Introduction Patients who had a mild ischaemic stroke who present with subtle or resolving symptoms sometimes go undiagnosed,are excluded from treatment and in some cases clinically worsen.Circulating immune cells are potential biomarkers that can assist with diagnosis in ischaemic stroke.Understanding the transcriptomic changes of each cell population caused by ischaemic stroke is critical because they work closely in a complicated relationship.In this study,we investigated peripheral blood mononuclear cells(PBMCs)transcriptomics of patients who had a stroke using a single-cell RNA sequencing to understand peripheral immune response after mild stroke based on the gene expression in an unbiased way.Methods Transcriptomes of PBMCsfrom 10 patients who had an acute ischaemic stroke within 24 hours after stroke onset were compared with 9 race-matched/age-matched/gender-matched controls.Individual PBMCs were prepared with ddSeqTM(Illumina-BioRad)and sequenced on the Illumina NovaSeq 6000 platform.Results Notable population changes were observed in patients who had a stroke,especially in NK cells and CD14+monocytes.The number of NK cells was increased,which was further confirmed by flow cytometry.Functional analysis implied that the activity of NK cells also is enhanced in patients who had a stroke.CD14+monocytes were clustered into two groups;dendritic cell-related CD14+monocytes and NK cell-related CD14+monocytes.We found CD14+monocyte subclusters were dramatically reduced in patients who had a stroke.Discussion This is the first study demonstrating the increased number of NK cells and new monocyte subclusters of mild ischaemic stroke based on the transcriptomic analysis.Our findings provide the dynamics of circulating immune response that could assist diagnosis and potential therapeutic development of mild ischaemic stroke.
